Solvent-dependent release of bromine from bromoquercetins

Quercetin, 6-bromoquercetin (3), and 8-bromoquercetin (4) undergo H/D exchange at 6- and 8-positions, in acetone-d6 and methanol-d4, catalyzed by acids and bases. The base-catalyzed process is faster, and in acetone- d6 the half-lives of H-8 and H-6 are 56.5 and 48.6 h, respectively. A high regioselectivity at the position 8 of quercetin is observed under acid-catalysis in both solvents but in methanol-d4 regioselectivity is retained even under base-catalysis. On the other hand, 6,8-dibromoquercetin (2), 4 and 6,8-dibromo-20- hydroxyquercetin (5) manifest the ability of exchanging bromine with hydrogen (or deuterium) under acid-catalysis in acetone and other enolizable ketones (e.g., methyl ethyl ketone, acetylacetone, and isophorone). These bromophenols release bromine from their 8-position only, in a slow bromination process that likely involves their protonated form (arenium ion I) as brominating agent and the enol of the above ketones as Br-acceptor. The arenium ion I of these bromophenols is expected to be a powerful electrophile and its formation is most likely to be rate-determining.